Routes of
administration Oral CAS Number 61422-45-5 Molar mass 257.261 g/mol | ATC code L01BC04 (WHO) PubChem CID 2577 | |
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AHFS/Drugs.com International Drug Names Synonyms 1-hexylcarbamoyl-5-fluorouracil, HCFU, N-hexylcarbamoyl-5-fluorouracil, Yamaful, NCGC00095165-01, Hexylcarbamoyl fluorouracil, 61422-45-5, UNII-HA82M3RAB2, CCRIS 2759, C11H16FN3O3, Uracil, 5-fluoro-1-hexylcarbamoyl-, BRN 0888898, HA82M3RAB2, 1(2H)-Pyrimidinecarboxamide, 5-fluoro-N-hexyl-3,4, | ||
Carmofur (INN) or HCFU (1-hexylcarbamoyl-5-fluorouracil) is a pyrimidine analogue used as an antineoplastic agent. It is a derivative of fluorouracil, being a lypophilic-masked analog of 5-FU that can be administered orally.
Contents
What does carmofur mean
Biology
Carmofur prodrug is ingested and taken up in the intestine, overcoming the problem of 5-FU degradation by dihydropyrimidine dehydrogenase. Once inside a cell, carmofur prodrug is converted into 5-FU.
Mechanism of action
The mechanism of action of carmofur prodrug is traditionally thought to be the generation of 5–FU. However, carmofur is a highly potent acid ceramidase (AC) inhibitor. Ceramide influences cancer cell survival, growth and death. Inhibition of AC activity sensitizes tumor cells to the effects of antineoplastic agents and radiation.
Medicinal uses
Product marketing for carmofur started in 1981. Carmofur has also been used as adjuvant chemotherapy for curatively resected colorectal cancer patients in China, Japan, and Finland for many years. Trials and meta-analyses have confirmed that the drug is effective on patients with this cancer type, extending their survival.
Brand name
Mifurol, Bayer, China; Carmofur, Japan
Adverse effects
As fluorouracil, carmofur has been known to induce leukoencephalopathy, characterized by progressive damage to white matter in the brain with stroke-like symptome.
A clinical trial for small hepatocellular carcinoma was stopped prematurely because 56% of the treated patients had unacceptable side effects. Moreover the treatment had no survival advantage for stage 1 and 2 cancer patients. This may be a reason why carmofur was never pursued for FDA-approval in the US.
Chemical synthesis
Ozaki et al. has reported carmofur synthesized by treating 5-FU with phosgene and hexylamine. Xiong et al. reported an alternative approach for carmofur synthesis. Chemical preparations and structures can be found here.